450R78101
5289
External Review Draft
April 1978
AN ASSESSMENT OF
THE HEALTH EFFECTS
OF COKE OVEN EMISSIONS
NOTICE
This document is a preliminary draft. It has been
released by EPA for public review and comment
and does not necessarily represent Agency policy.
U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
WASHINGTON, D.C. 20406
-------
External Review Draft
April 1978
AN ASSESSMENT OF
THE HEALTH EFFECTS
OF COKE OVEN EMISSIONS
NOTICE
This document is a preliminary draft. It has been
released by EPA for public review and comment
and does not necessarily represent Agency policy.
U.S. Environmental Protection Agency
Region V, Library
230 South Dearborn Street
Chicago, Illinois 60604
U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
WASHINGTON, D.C. 20406
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CONTENTS
Figures iii
Tables iii
Abbreviations v
Acknowledgment vi
1. Summary 1
2. Introduction 4
3. Composition, Particle Size, and Health 7
Effects
4. Experimental Evidence of Toxicity: 18
Carcinogenesis
Experiments with Animals 18
Metabolism of Polycyclic Aromatic 21
Hydrocarbons
5. Epidemiological Studies of High-level 25
Exposure
introduction 25
Historical Perspective 28
Recent Studies 33
6. Ambient Pollution and Respiratory Disease 53
7. Analysis of Health Effects 57
Introduction 57
Bioassay Results 60
Characterization Difficulties and 61
Health Effects
Bases for Interpreting Mortality Data 70
Estimating Health Effects from 73
Occupational Mortality Data
Estimating Exposure 79
Nonmalignant Respiratory Disease 89
Morbidity Statistics 92
Appendices
A. Selected Bioassay Results 100
B. Source and Concentration Data 107
References 119
U,S. Environmental Protection Agency
11
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FIGURES
Number Page
1 Dose-response relationships for mice and BaP 59
administered subcutaneously
2 Least-squares fits of BaP in benzene- and 69
cyclohexane-soluble fractions of total parti-
culate matter
3 Dose-response data for cumulative exposure to 81
CTPV's, nonwhite and white coke oven workers
4 ' Observed versus expected deaths from lung cancer 86
among coke plant workers as a function of
cumulative exposures, 1951-1966
TABLES
Number Page
1 Partial List of Constituents of Coke Oven 8
Emissions
2 Some Toxic Constituents of Coke Oven Emissions 9
and Some of Their Toxic Properties
3 Particle Size Range and Biological Significance 15
of Coke Oven Emissions
4 Temperature Range of Carbonizing Chambers and 26
Excess of Lung Cancer Reported
5 Summary of Epidemiological and Clinical Evidence 29
of Carcinogenicity
6 Summary of Mortality Data in Gas Workers 37
Observed by Doll
111
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CONTENTS (continued)
Number Page
7 Summary of Relative Risks of Death From Cancer 43
Among Coke Oven Workers
8 Summary of Epidemiological Studies of Long-Term 44
Mortality of Coke Plant Workers
9 Relative Risk for Lung Cancer as a Function of 64
Daily Tar Dosage from Cigarettes in Male Smokers
with Ten Years or More of Smoking
10 Partial List of Tumorigenic Agents and Other 65
Toxic Compounds in Coke Oven Emissions and in
Cigarette Smoke
11 Estimates of Average Annual Lung Cancer Mortality 76
• Rates
12 Approximate Relative Risks for the Nonsmoking 77
Population Estimated from Mortality Rates for
Coke Plant Workers
13 Estimated Cumulative Exposure to BaP and CTPV 84
and Corresponding Observed Mortality
14 Estimation of Equivalent Lifetime Dose for the 88
General Population
15 Observed Bronchitis Mortality 90
16 Correlations for Chronic Bronchitis Among Coke 95
Oven Workers
17 Chronic Bronchitis in the Coke Industry 98
IV
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A
AHH
BaP
BeP
BSF
BSO
CTPV
DBA
DMBA
MCA
PAH
POM
RR
SMR
TLV
TPM
ABBREVIATIONS
Aza-arene
Aryl hydrocarbon hydroxylase
Benzo(a)pyrene
Benzo (e)pyrene
Benzene-soluble fraction
Benzene-soluble organic
Coal tar pitch volatile
Dibenzanthracene
DimethyIbenzanthracene
Methylcholanthrene
Polycyclic aromatic hydrocarbon
Polycyclic organic matter
Relative risk
Standardized mortality ratio
Threshold limit value
Total particulate matter
Vim
ng
microgram
micrometer
nanogram
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ACKNOWLEDGMENTS
This document was prepared by EPA's Office of Research
and Development with extensive help from a team of consul-
tants led by Jeanne M. Stellman, Ph.D. Major contributors
are Geoffrey Kabat, Ph.D., and Dietrich Hoffmann, Ph.D.
The final document will in addition incorporate, as
appropriate, comments and contributions from many sources,
and especially those from EPA's Scientific Advisory Board.
vi
-------
A
AHH
BaP
BeP
BSF
BSO
CTPV
DBA
DMBA
MCA
PAH
POM
RR
SMR
TLV
TPM
ABBREVIATIONS
Aza-arene
Aryl hydrocarbon hydroxylase
Benzo(a)pyrene
Benzo(e)pyrene
Benzene-soluble fraction
Benzene-soluble organic
Coal tar pitch volatile
Dibenzanthracene
Dimethylbenzanthracene
Methylcholanthrene
Polycyclic aromatic hydrocarbon
Polycyclic organic matter
Relative risk
Standardized mortality ratio
Threshold limit value
Total particulate matter
ym
ng
microgram
micrometer
nanogram
v
-------
ACKNOWLEDGMENTS
This document was prepared by EPA's Office of Research
and Development with extensive help from a team of consul-
tants led by Jeanne M. Stellman, Ph.D. Major contributors
are Geoffrey Rabat, Ph.D., and Dietrich Hoffmann, Ph.D.
The final document will in addition incorporate, as
appropriate, comments and contributions from many sources,
and'especially those from EPA's Scientific Advisory Board.
VI
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SECTION 1
SUMMARY
1. Coke oven emissions consist of a complex mixture of
substances that are etiologically implicated in increased
mortality from a variety of malignant and nonmalignant
diseases among various populations of workers exposed to
them for varying lengths of time. These risks include the
following:
a. Elevated risk for cancer of all sites (relative
risk [RR] 1.62; p<0.01; Redmond, 1976).
b. Elevated risk for respiratory cancer (RR 15.7;
p<0.01; Redmond, 1976).
c. Elevated risk for kidney cancer (RR 5.0; p<0.01;
Redmond et al, 1976).
d. Elevated risk for gastrointestinal cancer: large
intestine and pancreas (RR 2.93, p<0.01 — intes-
tine; RR 4.55, p<0.01 -- pancreas; Redmond et al,
1976).
e. Elevated risk for pharyngeal and buccal cancer (RR
3.87; p<0.01; Redmond et al, 1976).
f. Elevated risk for nonmalignant respiratory disease
(at least 2-fold excess, Redmond, 1976).
Among lightly exposed workers (nonoven workers in coke
plant) an increased risk for nonmalignant respiratory
disease and cancer of several sites was also observed.
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2. Although workers exposed to the emissions develop
malignant and respiratory diseases at an elevated rate, they
enjoy a favorable overall mortality as a group, in compari-
son with the general population, a common observation in the
study of occupational medicine. Thus the general popula-
tion, which includes the young, the old, and the infirm,
should be considered more susceptible than the work force,
especially for development of chronic bronchitis, since they
are generally in poorer health.
3. Coke oven emissions contain an array of identified
carcinogens, irritants, particulate matter, trace elements,
and other chemicals. The toxic effects observed in both
humans and animals are greater than the effects that can be
attributable to any individual component. This fact sug-
gests an interplay'of factors such as cocarcinogenesis,
tumor initiation, and tumor promotion that are involved in
exposure to "coke oven emissions" as a whole. Thus the
emissions as a whole should be considered the toxic agents,
and it is inappropriate simply to attribute toxicity of the
emissions to any particular component such as benzo(a)pyrene
(BaP), although BaP may serve as a useful chemical tool for
approximating overall exposure.
4. Extrapolations and approximations derived from occupa-
tional data afford the crude estimate that there is an ex-
posure difference of about 2 orders of magnitude between
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lightly exposed workers and people living in the vicinity of
coke plant, as indexed by BaP concentrations. Since these
lightly exposed workers show an elevated risk for cancer and
nonmalignant respiratory disease, it is reasonable to assume
that levels up to one-hundreth of those to which lightly
exposed workers are subjected could cause an increased risk
to the general population.
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SECTION 2
INTRODUCTION
A substantial body of evidence, both direct and in-
direct, indicates that coke oven emissions, a complex mix-
ture of many components, are carcinogenic and toxic. The
carcinogenic potential of various fractions of coal-tar-
pitch volatiles (CTPV's), which are a major constituent of
coke oven emissions, and of benzo (a)pyrene (BaP), a car-
cinogenic constituent of the volatiles, has been established
by laboratory studies. Epidemiological findings among coke
oven workers show that coke oven emissions are carcinogenic
to humans and also can lead to the development of nonmalig-
nant respiratory disease, such as chronic bronchitis and
emphysema. Chronic lung disease is a serious, irreversible
condition that is often debilitating and can be fatal.
Th6 epidemiological evidence relating to other coal
carbonization processes, such as those involved in commer-
cial gas production, and to cigarette smoke is also relevant
here because of congruence between many of the constituents
of coke oven emissions and the constituents of gas works
effluents, tobacco smoke, and other sources of combusted
-------
organic matter (National Academy of Sciences, 1972). All of
these effluents contain polycyclic organic matter (POM), as
well as a wide variety of other chemicals.
Our evaluation in this study of the evidence relating
to health hazards of other combustion products confirms that
the array of toxic effects observed in cigarette smokers and
gas-industry workers is similar to the effects qbserved
among coke oven workers. In particular, the finding that
cigarette smoke and coke oven emissions contain very similar
compounds capable of inducing cancer in humans and animals
is of significance and can be considered evidence of the
carcinogenicity of coke oven emissions. Additional indirect
evidence comes from data that support an association between
urban air pollution and incidence of chronic bronchitis and
possibly of lung cancer (Goldsmith and Friberg, 1977), since
polluted urban air also contains, in addition to other
materials, compounds found in cigarette smoke and coke oven
emissions.
It is important that the effects described throughout
this report be regarded as resulting from the complex mix-
ture that constitutes coke oven emissions and not from any
particular components such as BaP or the benzene-soluble
fraction (BSF) of total particulate matter, components that
often serve as indicators of the emissions. As we will
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show, there is extensive evidence that the effects observed
are greater than the sum of effects that could be attributed
to individual components. Further, the mixture is not
accurately definable by any particular component.
The purpose of this report is to use the different
bodies of available evidence in assessing the magnitude of
the health effects of coke oven emissions on the population
at large.
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SECTION 3
COMPOSITION, PARTICLE SIZE, AND HEALTH EFFECTS
Coke oven emissions include all of the constituents of
bituminous coal released into the atmosphere during the pro-
cess of carbonization. Among these constituents are a
number of carcinogens; at least one, B-naphythylamine, is a
proven human carcinogen (Mancuso, 1967). Toxicity of coke
oven emissions also is manifest in respiratory irritation,
cocarcinogenesis, tumor promotion, and other toxic effects.
Table 1 shows a partial list of the constituents of coke
oven effluents, and Table 2 summarizes some noncarcinogenic
toxic effects, such as skin irritation and irritation of the
upper respiratory tract. Appendix B gives some of the
levels of various constituents that have been measured.
In addition to chemical composition, the form in which
the various constituents are released into the atmosphere
(e.g., aerosols, gases) and the size and density of the par-
ticulate matter with which they are associated determine
their effects on human health. Most of the particles emit-
ted are in the respirable range, which means that they can
penetrate into the lungs past the normal respiratory defense
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Table 1. PARTIAL LIST OF CONSTITUENTS
OF COKE OVEN EMISSIONS
WLYNUCLEAR AROMATIC HYDROCARBONS*
Anthanthrene
Anthracene
•enzindene b
Benz (a) anthracene ,
Benzo (b) fluoranthem b
••nzo (qhi) fluoranthene
•enzo (j) fluoranthene
Benzo (k) fluoranthene
Benzofluorene
•enzo (a) fluorene
•enzo (b) fluorene
•enzo (c) fluorene
•enzophenanthrene
•enzo (ghi) perylene
Benzo (a) pyrene
•enzo (e) pyreneb
Benzoquinoline
Chryiene
Coronene b
Oibenz (ah) anthracene
Dibenio (ah) pyreneb
Dihydroanthracene
Dihydrobenzo (a) fluorene
Dihydrobenzo (b) fluorene
Dihydrobenzo (c) fluorene
Dihydrobenz (a) anthracene
Dihydrochrysene
Dihydrofluoranthene
Dihydrofluorene
Dihydromethylbent (a)
anthracene
Dihydromethlybenzo
(k and b) fluoranthenes
Dihydromethylbenzo
(a and e) pyrenes
Dihydrome thy Ichry cent.
POLYNUCLEAR AZA-HETEROCYLIC
COMPOUNDS*
Acridine b
Benz (c) acridine
Dibenz (a,h) acridine
Dibenz (a,j) acridine
AROMATIC AMINESb
(-Naphthylanine
a-Naphthylatnine
OTHER AROMATIC COMPOUNDS
Benzene
Phenol=d
Toluene
Xylened
Dihydromethyltriphenylene
Dihydrophenanthrene
Dihydropyrene
Dihydrotriphenylene
Dimethylbenzo (b) fluoranthene
Dimethylbenzo (k) fluoranthene
Dimethylbenzo (a) pyrene
Dimethylchryiene
Dimethyltriphenylene
Ethylanthracene
Ethy Ipherv nthrene
Fluoranthene
Fluorene
Indeno (1,2,3-cd) pyrene
Methylanthracene
Methylbenz (a) anthracene
Methylbenzo (a) pyrene
Methylbenzo (ghi) perylene
Methylehrysene
Methylfluoranthene
MethyIfluorene
Methylphenanthrene
Methylpyrene
Methyltriphenylene
Octahydroanthracene
Octahydrofluoranthene
Octahydrophenanthrene
Octahydropyrene
Perylene
Phenanthrene
o-Phenylenepyrene
Pyrene
Triphenylene
TRACE ELEMENTSb
Arsenic
Benyllium
Cadmium
Chroniuiti
Cobalt
Iron
I*ad
Nickel
Selenium
OTHER CASES
Ammoniac
Carbon dilulfide
Carbon monoxide0
Hydrogen cyanide^
Hydrogen tulfide
Methanec ..
Nitric oxide
Sulfur dioxide
* l*o «t al (1I7S), except at noted.
b Komreich (1*76).
e teith (1*71).
6 White (1*75).
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mechanisms. Particles ranging from 0.1 to 2 ym in diameter
are the optimum size for such penetration and hence are the
most biologically significant. After entering the respira-
tory tract they are largely retained in the trachea, bronchi,
and alveoli. Particles larger than 2.0 ym are trapped by
the mucous membranes and do not enter the lungs. Particles
smaller than 0.1 ym are retained in the tracheobronchial
tree but elution does not occur. Particles smaller than
0.04 ym do not come out of suspension in the inhaled air and
are exhaled (Falk and Kotin, 1961). In the atmosphere
polycyclic aromatic hydrocarbons (PAH's) are primarily found
absorbed on particulate matter, hence the prep^.nce of
respirable particulate matter increases the likelihood that
PAH's will penetrate into the lungs. Table 3 gives the
range of particle sizes found in coke oven emissions.
The trapped particles in the mucus that are not exhaled
and that also do not enter the lung are either swallowed or
spit out. Morgan (1975) hypothesizes that in asbestos ex-
posure it is the swallowing of asbestos-containing mucus
that leads to the increased incidence of neoplasia of the
digestive organs. Elution of PAH's from swallowed particle-
contaminated mucus may also explain the diverse sites of
cancer associated with exposure to coke oven emissions.
14
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15
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Elution of the PAH's requires a sufficient period of
contact between the soot particles and the respiratory
epithelium. The larger the particle (provided that it is
respirable), the more readily elution into the lungs takes
place. PAH's that are adsorbed onto particles smaller than
0.1 ym are not readily eluted (Falk and Kotin, 1961).
Furthermore, mucociliary defense clearance mechanisms that
normally may limit the entrance of respirable materials are
hampered by some chemical and physical agents present in
coke oven emissions.
.In addition to evidence of the carcinogenic properties
of substances like PAH's and aza-arenes, various substances
in coke oven emissions are known to produce noncarcinogenic
toxic effects, such as nonmalignant respiratory disease,
which is discussed later. Many of the major toxic constitu-
ents of coke oven emissions (Table 2) are irritants and
cilia-toxic agents; some are thought to be cocarcinogens.
Sulfur dioxide and sulfuric acid mist are known to cause
irritation of the respiratory tract, interfere with mucous
clearance mechanisms, and produce bronchoconstriction, as
reflected by increased airway resistance. Sulfur dioxide is
readily converted into the more powerful irritant, sulfuric
acid, in the presence of humidity and particulate matter
(Andur, 1969). Hydrogen cyanide is also strongly cilia-
-------
toxic and imicus-flow-inhibiting. Most toxicological re-
search on these noncarcinogenic constituents of coke oven
emissions has been concerned with exposure to the individual
substances alone. We can only guess at the combined toxic
potential of the several components as they occur in coke
oven emissions.
17
-------
SECTION 4
EXPERIMENTAL EVIDENCE OF TOXICITY: CARCINOGENESIS
EXPERIMENTS WITH ANIMALS
Over the past few decades, both in vivo and in vitro
studies have helped establish the carcinogenicity of par-
ticular PAH's. With regard to the potential carcinogenic
hazard to humans of PAH's in coke oven effluents, the most
pertinent data stem from experiments with animals involving
cutaneous application, intratracheal instillation, and in-
halation exposure. These methods of administration most
resemble the routes by which humans may be exposed to PAH's,
and the studies also have helped elucidate the role of
synergism among different pollutants in the production of
cancers.
Cutaneous application on mouse skin is an important
bioassay method used as a model system for studying histo-
logical changes associated with precarcinogenic and carcino-
genic stages. Carcinogenic activity on mouse skin has been
demonstrated for various tars, soots, oils, urban air pollu-
tants, gasoline and diesel engine exhaust "tars," the par-
ticulate matter of tobacco mainstream and sidestream smoke,
18
-------
and several other combustion products (Wynd'jr and Hoffmann,
1976; Karbe and Park, 1974; Kipling, 1976; Hoffmann and
Wynder, 1977). Studies of fractions of environmental in-
halants have, demonstrated that the major type of carcinogen
in organic air particu.lates is the PAH, and that aza-arenes
contribute carcinogenic activity to a lesser degree (NAS,
1972) .
Laskin et al (1970) showed the importance of synergism
between two of the most common pollutants in air - S02 and
BaP - in respiratory carcinogenesis. When rats were exposec
to the irritant SO- alone, they developed hyperplastic and
meta-plastic aberrations. But when S0~ exposure was com-
bined with BaP exposure (by inhalation), the rats developed
squamous cell carcinomas of the bronchus. It has been
postulated that SO- synergism slows ciliary action and
therefore increases BaP retention and/or causes chronic
injury; following injury the resultant regenerating cells
may be more susceptible to the BaP (Scala, 1975).
Synergism has also been demonstrated between carcino-
genic chemicals and particulate matter (for example, carbon
and iron oxide). In a study by Saffiotti et al (1968) , all
of the hamsters that were administered a 50:50 mix of BaP
and iron oxide developed tumors of the respiratory tract,
whereas none of the hamsters given iron oxide or BaP alone
19
I
-------
developed any lung tumors. The tumors induced in the
hamsters were comparable to those found in humans, both in
histological type (squamous cell and anaplastic carcinoma
were most frequent) and in location in the respiratory tract
(largely from the epithelium of the major bronchi or their
primary divisions). A sequence of tumor development from
hyperplasia to squamous cell metaplasia was observed.
Montesano et al (1970) performed experiments of a
similar type, also with Syrian hamsters, using intratracheal
instillation of BaP and iron oxide. In a dose-response
study, four groups of hamsters were given weekly administra-
tions of different doses of a BaP/iron oxide mixture. The
groups received 2.0, 1.0, 0.5, and 0.25 mg of BaP, each with
an equal amount of iron oxide. The results showed a defi-
nite, positive correlation of dose level and tumor inci-
dence. Also, the greater the dose level, the earlier the
tumors appeared. Other studies indicated that a given total
quantity of BaP/iron oxide mixture administered in fractions
by frequent instillations would produce tumors earlier than
a single administration of the total dose. Again, the
morphology and topography of these experimentally induced
tumors were markedly similar to those in humans.
Crocker et al (1970) have demonstrated that intra-
tracheal instillation of a BaP/iron oxide mixture can induce
respiratory tract tumors in a primate, Galago crassicaudatus.
20
-------
Black ink powder has been used as the carrier for carcinogens
in intratracheal instillation studies. L. M. Shabad (1962)
induced bronchogenic carcinomas in rats using dimethyl
benzanthracene (DMBA) on black ink powder.
Other animal studies, particularly those involving
mouse skin, have suggested a two-stage mechanism for tumor
induction, in which PAH's act as tumor initiators and
phenols, aliphatic hydrocarbons, 3- and 4-ring PAH's, and
dihydroxybenzenes act as tumor promoters (Van Duuren, 1969).
As in cocarcinogenesis, the initiation-promotion model is
based on the combined action of different compounds to pro-
duce' an effect that no single compound would produce by
itself. The indication in laboratory experiments that dif-
ferent components of coke oven emissions interact synergis-
tically lends support to the view that the toxic potential
of the complex mixture — coke oven emissions -- cannot be
related to the potential of a single compound.
METABOLISM OF POLYCYCLIC AROMATIC HYDROCARBONS
In recent years much research has been conducted to
clarify the metabolism of carcinogenic PAH's. Maximum
systemic excretion of BaP ana its metabolites is via the
liver and biliary system (Heidelberger and Jones, 1948;
Kotin et al, 1959) . There is a maximum excretion rate into
the bile in rats suggestive of numerous storage sites.
21
-------
Adipose tissues, the central nervous system, and the seba-
ceous glands have been identified as storage sites (Chalmers
and Peacock. 1936; Peacock, 1936).
It is the metabolic pathways of PAH's that are of
interest. Brooks and Lawley (1964) reported that there is
no binding of a PAH to any cellular constituents immediately
after application of PAH's to the skin, but rather that the
maximum amount of binding occurs only after an interval of
24 to 48 hours. This finding strongly suggests that meta-
bolic activation is a prerequisite for macromolecular
binding of PAH's. Gelboin (1969) found that binding of BaP
to DNA in vitro depended upon the presence of rat liver
microsomes, since without the microsomes no binding would
occur. It is hypothesized that the aryl hydrocarbon hydrox-
ylase (AHH) system in the microsome fraction of rat liver
cells can "activate" the PAH's (Gelboin and Wiebel, 1971).
Elucidation of metabolic pathways is thus essential,
since the parent polycyclic hydrocarbons are largely chemi-
cally inert. Current studies are working out in detail the
biochemical conversion of BaP to its carcinogenic metabo-
lite(s) (e.g., Levin, 1977), which are thought to result
from activation by the microsomal monoxygenase system
(Miller and Miller, 1974; Jerina and Daly, 1974; Sims and
Grover, 1974; Gelboin, Kinoshita, Wiebel, 1972). The recent
22
-------
SECTION 5
EPIDEMIOLOGICAL STUDIES OF HIGH-LEVEL EXPOSURE
INTRODUCTION
In attempting to assess the health effects of high-
level exposure to coal-tar pitch volatiles, investigators
have done epidemiological studies involving coke-oven
workers as well as workers employed in the production of gas
for household use ('town-gas') and for industrial use (gen-
erator gas).* The inclusion of mortality data relating to
these different processes is warranted by the earlier-
mentioned similarity of the chemical processes and effluents
involved in coal gasification and in coking. The relative
proportions of the various constituents in the different
processes vary with the temperature of carbonization and
with the type of coal used. Epidemiological evidence of
greater increases in disease rates among workers exposed to
the higher-temperature processes suggests that the higher
the temperature of carbonization, the higher the proportion
of toxic compounds released (see Table 4).
*
Coke-plant data come mainly from the United States, Russia,
and Czechoslovakia; coal gasification plant data come from
Europe and Japan.
25
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Exposure data on retort house gas workers and coke oven
workers show that the concentrations of pollutants are of
the same order of magnitude. Lawther et al (1965) measured
the concentrations of BaP and other PAH's (BeP; 1,12 benz-
perylene; coronene) in gas works retort houses. The repre-
sentative mean concentrations of BaP in tarry fumes escaping
from the retorts for long-period samples (collected with a
continuous sampler over periods of 2 to 4 weeks) averaged 3
yg/m . The maximum was in the same range as the levels to
which coke-oven workers are exposed. In samples obtained
with.personal monitors the average BaP concentration was 2.6
yg/m , which is approximately equivalent to 0.26 mg/m of
the benzene-soluble fraction of total particulate matter
[taking BaP as 1% of the benzene-soluble organics (BSD), as
calculated by Schulte et al, 1975] and is comparable to the
threshold limit value (TLV). All particles in the gas
retort houses were respirable (within the range of 0.1 to
1.0 um).
A major difference between the coking process and the
coal gasification process appears to be the relative absence
of S02- in the latter (0.35 ppm) (Lawther et al, 1965).
Absence of S02 would lead one to expect that rates of lung
cancer among gas workers would be lower than those among
coke oven workers, since S02 is believed to have a syner-
27
-------
gistic effect on carcinogenesis, as demonstrated experi-
mentally (Laskin et al, 1970). A similar synergistic
relationship with SC^ has been hypothesized for arsenic
exposure (Lee and Praumeni, 1969) . Another difference is
that more workers labor on or near the top side of coke
ovens and hence are heavily exposed to the effluents, where-
as only the top man in a horizontal retort .house has the
highest exposure. The effluent mixture itself varies with
temperature of carbonization, the higher temperatures
apparently leading to a more carcinogenic mixture. Compari-
son of the lower relative mortality of gas retort workers
reported by Doll (1952, 1965, 1972) with data in an ongoing
long-term study (e.g. Lloyd, 1971) of the mortality of
steelworkers and coke oven workers seems to bear out these
hypotheses.
HISTORICAL PERSPECTIVE
Epidemiological studies in different countries have
demonstrated that workers exposed to the products of the
combustion and distillation of bituminous coal experience an
increased incidence of cancer of several sites (lung,
pancreas, kidney, bladder, skin). These studies are dis-
cussed below, and the overall results are summarized in
fable 5.
28
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Buccal an
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31
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The earliest association of skin cancer with occupa-
tions involving exposure to coal-combustion products was
that of Percival Pott, who in 1775 observed the high in-
cidence of scrotal cancer among chimney sweeps exposed to
soot. His observation has now become a classic reference of
occupational medicine for cancer and for discussions of coal
tar products. In the early 20th century several studies
established the association (Sladdin, 1928; Bridge and
Henry, 1928; E. L. Kennaway, 1925). Kennaway and Kennaway,
in a later series of reports, found an increased rate of
bladder and lung cancer in occupations involving exposure to
coal gas, tar, pitch, and soot (1931, 1936, 1947). In their
study of cancer of the bladder and prostate, Henry, Kennaway,
and Kennaway (1931) found that workers in 8 out of 10 occu-
pations involving exposure to coal products showed an in-
creased risk of bladder cancer as compared with the general
English male population. For 5 out of 10 occupations the
risk was- 1-1/2 to 4 times greater. Among 46 occupations
examined, the three occupations with the highest risk of
bladder cancer were patent-fuel workers, gas works engine
and crane drivers, and tar-distiller workers. In a later
retrospective study of the incidence of cancer of the lung
and larynx in England and Wales from 1921 to 1932, Kenneway
and Kenneway (1936) noted an excess lung cancer mortality
32
-------
among British gas workers and other coal carbonization and
by-product workers. In this and a follow-up study (1947)
covering the period 1921 to 1938, Kenneway and Kenneway
noted an excess of lung cancer deaths among gas producermen,
chimney sweeps, and certain categories of gasworks employees,
Data on "gas stokers and coke oven charges" showed an
approximately 3-fold excess. Doll (1952) comments that
these findings are "suggestive of a special occupational
risk" but are not conclusive "because the numbers of men
engaged in the various occupations had to be deduced from
the evidence provided by the censuses of 1921 and 1931 and
were not known with any certainty after the latter date."
Another important report was a study by Kuroda demon-
strating a high incidence of lung cancer among Japanese gas
generator workers. Although lung cancer was a relatively
rare form of cancer in Japan during the 1930's, accounting
for 3.1 percent of all cancer, this study showed that lung
cancer accounted for 80 percent of all cancer among the gas
generator work force who were exposed to extremely high
quantities of material similar to coke oven emissions.
RECENT. STUDIES
In another study of 504 deaths among former gas workers
at a Japanese steel plant, Kawai et al (1967) found 6 deaths
from lung cancer in contrast with the expected number,
33
-------
0.180, for other workers at the same plant with no gas-
generator work experience; this value is 33 times the ex-
pected rate. Age-standardized mortality from lung cancer in
the control group was close to that of the general male
population. The large excess of lung cancer deaths among
the gas workers could not be attributed to smoking. The
authors note that the excess of lung cancer mortality
occurred only in the age group of 45 to 54 years. Data for
those in this group with 10 to 19 years of gas-generator
work experience showed a marked increase in lung cancer
risk, whereas data for those under 45 years of age with the
same work experience (10 to 19 years) showed no signifi-
cantly excessive mortality. The implications of this
finding are discussed in Section 7.
Bruusgaard (1969) studied 125 deaths among former gas
works employees in Norway, all of whom had at least 5 years
work experience and most of whom had more than 10 years.
The number of respiratory cancers was higher than expected
(12, or 9.6% of the total number of deaths, against 1.5% in
males for the country as a whole). The proportion of lung
cancers to cancers of all sites among the gas workers
(29.2%) was also significantly higher than that in the
general population, 9.2 percent. In addition, there were 5
deaths from cancer of the bladder — 12 percent of all
34
-------
cancers. Although Bruusgaard gives no exposure data and
occupational histories for most cases are incomplete, he
notes that workers with a history of employment in the
retort houses had an especially high incidence of respira-
tory cancer.
Reid and Buck conducted a mortality study in 1956 among
800 coke plant workers randomly selected from a total of
8000 employed over the years 1949-54, inclusive. The study
did not show an elevated cancer risk when death rates for
all causes and for cancer were compared with age-specific
rates prevailing in the period 1950-54 among workers in a
large unspecified industrial organization. The cause of
death was ascertained either by reference to the union's
funeral fund records, which were required to be supported by
a copy of the death certificate, or by a special search at
the General Register Office. The coke plant workers were
categorized by occupation: coke-oven workers, those handling
by-products, and maintenance workers (further grouped as
laborers, workers, and foremen). No total excess in the
number of cancer deaths was found among the coke plant
workers as a whole, and there was a "complete lack" of any
excess of respiratory cancer for men working on the ovens.
When occupational history was taken into account, no ex-
cessive cancer risk was found for by-product workers and
35
-------
only a small excess was found for men who had at some time
worked at the oven.
This study was criticized by Lloyd (1971), who pointed
out that Reid and Buck may have underestimated the number of
lung cancer deaths since the records included only men dying
while still "on the books" during the period 1949-54. .Lloyd
also states that "the population at risk and the distribu-
tion by age and area of prior employment was based on an
estimate of figures which excluded retirees and those who
had left employment." Although employment history is in-
adequate and followup is incomplete, reanalysis of Reid and
Buck's data shows that the only occupational group with an
excess for all cancer as cause of death was the oven-worker
group. A higher death rate of the top-side workers probably
would be diluted in this study, since Reid and Buck's
definition of oven workers includes both top-side and side-
oven workers.
In an effort to further quantify the Kennaway and
Kennaway data suggesting a correlation between occupational
exposure and cancer mortality, Doll (1952) studied the mor-
tality among male pensioners (over age 60) of a large London
gas works company for a 10-year period (1939-1948) and
compared the data with mortality data for the population of
Greater London. Table 6a, which summarizes the results of
36
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this study, shows that retired gas workers had a statisti-
cally significant excess of lung cancer deaths as compared
with the number of deaths expected at the London rates. In
this study, data on men who retired early were included when
the men reached age 60 so as not to bias the investigation
by the exclusion of a particularly unhealthy group who
retired early because of health reasons. Age-standardized
mortality ratios were calculated by use of mortality rates
for England and Wales, which were weighted to approximate
higher rates in Greater London. The causes of death recorded
by the company had been copied from death certificates. The
pensioners' mortality from all causes was close to the
expected (840 deaths against 856 expected), but the mor-
tality from cancer was in excess of the expected (156
against 123.5; p<0.01). Cancer of the lung accounted for
the greatest excess (25 against 10.4; p<0.001) which con-
stitutes a significant increase in mortality.
To assess differences in risk among different jobs
within the gas works, Doll categorized the pensioners as
those employed outside the works and those involved directly
in the production of gas or in handling of the waste prod-
ucts, representing a low- and a high-exposure group, re-
spectively. Excess lung cancer among the high-exposure
group was significant (17 observed versus 8.6 expected,
39
-------
0.01
-------
cla«c«e according to their exposure: heavy exposure (A);
int«rnitt«nt exposure (B); minimal exposure, or exposure
only to by-products (C). Again, elevated mortality was
attributed to respiratory system disease, specifically,
cancer of the lung and bronchitis. The lung cancer mor-
tality rate was 69 percent higher for Class A than for Class
C. A 4-fold higher rate of bladder cancer was also observed
in Class A as compared with Class C. The increase in
bladder cancer verged on significance (p=0.06) according to
Doll, who concluded that the mortality of gas workers varied
significantly with the type of work and that mortality was
highest among workers with greatest exposure to the products
of coal carbonization. A report on an additional 4 years of
observation of the cohort (Doll, 1972) provided follow-up
information on 2449 coal-carbonizing process workers and 579
maintenance workers on mortality rates gathered at annual
intervals from 1961 to 1965. Additional employees of four
other, gas boards were also followed over periods of 7 to 8
years.
Heavily exposed workers (Class A) experienced a highly
significant elevated mortality from lung cancer (p<0.001)
and bronchitis (p<0.001). Data on by-product workers (Class
C) show no excessive mortality and over the 12-year period
provide no substantial evidence of increased occupational
41
-------
risk for this group. The additional 4 years of data in this
study support the earlier association between exposure to
the products of coal carbonization and increased lung cancer
and also a risk of bladder cancer (p=0.06). However, the
increased mortality from bronchitis, noted earlier, was no
longer apparent.
An important series of reports on the mortality of coke
oven workers is the extensive, ongoing study of steelworkers
conducted by Lloyd, Redmond, et al at the University of
Pittsburgh. These reports, the results of which are sum-
marized in Tables 7 and 8, indicated increased relative
risks for certain cancers among coke oven and nonoven coke
plant workers. In the course of their study of mortality
among nearly 60,000 steelworkers, these investigators began
to concentrate on coke oven workers as a subgroup within the
steelworker population apparently because of the observed
elevated mortality of that subgroup from respiratory and
other cancers. This work has confirmed and extended the
well-established findings that workers exposed to the coal-
carbonization process experience a markedly increased cancer
risk. The successive phases of this study also show in-
creased cancer response rates with increased exposure and
dose. The results of these studies and available cumulative
exposure data are discussed in detail below, along with
42
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potential health effects at lower-level exposures, which
were approximated within the constraints of the data.
The coke plant workers studied by Lloyd were employed
in by-product coke plants. In contrast to the older beehive
coke oven, which released the volatile matter (by-products)
into the atmosphere, the by-product oven recovers most of
the tar, oil, and chemicals from the volatiles. Exposure to
effluents from by-product coke ovens is due to the escape of
volatiles during charging, quenching, and discharging and to
their escape through improperly sealed openings.
In these studies the workers were classified by work
area-within the plant in terms of function and exposure to
effluents, a task made difficult by the variety and vague-
ness of job titles used in occupational histories by dif-
ferent companies and changes in titles over long periods of
time. The by-product coke plant was therefore analyzed in
terms of three distinct areas: 1) the coal-handling area,
2) the coke oven area, and 3) the by-products plant for
recovery of gas and chemical products (areas 1) and 3) are
nonoven workers). Since earlier work (e.g. Doll, 1972;
Kennaway and Kennaway, 1936, 1947) had shown no apparent
increased cancer risk for men involved in work similar to
that performed in areas 1) and 3), some of the initial study
groups included only those workers employed in area .1) .
45
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In this long-term study, Lloyd (1971) examined the
mortality records of the workers in relation to length of
employment and work area within the coke plant and compared
the cause-specific mortality of coke plant workers as a
whole with the mortality of the total steelworker popula-
tion. Thus he eliminated the difficulty of comparing non-
workers with supposedly healthier workers. The cohort for
the study included all men employed in two of the three
Allegheny County steel plants operating coke plants during
1953. - Coke plant workers were categorized as oven workers
and nonoven workers. In this phase of the study, the excess
mortality from respiratory cancer among all coke plant
workers employed in 1953 could be accounted for by the
excess mortality of workers employed on the coke oven itself
(20 observed, 7.5 expected).
The excess mortality of coke oven workers was further
demonstrated when men employed at the ovens before 1953 were
included in the coke oven worker category. This inclusion
added 84 deaths and increased the mortality rate by 84
percent. Deaths among men employed in 1953 accounted for 13
of the 33 deaths observed from respiratory neoplasms, more
than twice the expected number. In total, the current plus
the former coke oven workers experienced a 2-1/2-fold excess
mortality from respiratory cancer.
46
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Although the initial study also showed a difference
between white and nonwhite workers, this difference resulted
from too few white workers and disappeared later when more
white workers were added to the study. Further, a signifi-
cant excess of cancers of the digestive system was observed
in nonoven workers employed in 1953 and prior years (17 vs.
9.7 expected; significant at the 5% level). Cancer of the
pancreas and large intestine showed the greatest excess.
The results of this first study showed the importance
of analyzing mortality by job classification, indicative of
relative exposures, and by length of exposure. Deaths among
full-time top-side workers accounted for all of the excess
mortality of coke oven workers from all causes and almost
all of the mortality from lung cancer. Deaths from lung
cancer among full-time top-side workers were 7 times the
expected rate (19 vs. 2.6; significant at the 1% level).
Lloyd comments that because the population was followed for
only 9 years, his estimates of lung cancer mortality may be
conservative owing to the long period of latency in occu-
pational lung cancers (15 to 25 years), a comment borne out
by the continuing studies.
Elevated rates in mortality of coke oven workers from
all causes of death were associated with length of employ-
47
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ment. Excess mortality among men employed at the ovens less
than 5 years was slight, whereas among those employed more
than 5 years the overall mortality was 17 percent higher
than expected and the lung cancer death rate was 3-1/2 times
that expected. These findings can be interpreted as pre-
liminary evidence for a dose-response relationship between
respiratory cancer and exposure to-coke oven emissions.
Total mortality of men employed 5 or more years at full-time
top-side jobs was twice the expected value (35 vs. 17;
significant at the 1% level). Almost all of this increase
was due to a 10-fold risk of lung cancer for full-time top-
side workers (15 vs. 1.5; significant at the 1% level).
Redmond et al (1972), in a follow-up of earlier reports
in the series, examined the mortality records of cohorts of
coke oven workers in an expanded study at 12 steel plants.
In addition, the data from the earlier study (1971) of two
Allegheny County plants were updated from 1961 to 1966 and
were compared with data from ±0 other plants for the same
period. The cohorts, at the 10 additional plants included
all men who had worked at the oven at any time in the 5-year
period.1951 through 1955. (The criterion for inclusion in
the prior Allegheny County study was employment in one of
the two coke plants during 1953).
48
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The findings of Redmond et al indicate that both the
level and duration of exposure to coke oven emissions are
correlated with mortality from various types of cancer. The
additivity of time and dose was further substantiated.
Analysis of mortality by cause shows significantly elevated
mortality of coke oven workers from- malignant neoplasms (RR
1.34; p<0.01), from malignant neoplasms associated primarily
with respiratory cancer (RR 2.85; p<0.01), from kidney
cancer (RR 7.49; p<0.01), and from prostate cancer (RR 1.64;
not significant).
Initial analysis showed a discrepancy between the risks
of white and nonwhite coke oven workers until data on
relative exposure by race were analyzed. The data showed
that 41.5 percent of the nonwhites and 29.8 percent of the
whites had been employed at the coke ovens for 5 or more
years at the time of entry to the study. Only 2.2 percent
of the whites had been employed full-time top-side and 11.2
percent were employed part-time top-side; in contrast, 27.3
percent of the nonwhites were employed full-time top-side.
Since top-side work entails the heaviest exposure to coke
oven emissions, the exposure of nonwhite workers clearly is
disproportionately heavy relative to that of white workers.
The study showed that men employed at full-time top-
side jobs for 5 years or more have a relative risk of lung
49
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cancer of 6.87 (p<0.01) as against risks of 3.22 (p<0.01)
for men with 5 years of mixed top-side and side-oven ex-
perience and 2.10 (p<0.05) for men with 5 or more years
side-oven experience. These data indicate a definite
gradient in response based on both type and duration of
exposure. When relative exposures and responses are a-
ccounted for, the racial differences are lost.
Overall, the study confirmed the Lloyd findings of a 2-
1/2-fold excess of mortality from respiratory cancers. A
new finding of Redmond's was a significant excess of kidney
cancer among coke oven workers (RR 7.49; p<0.01).
Redmond concludes that the 6.87 (p<0.01) relative risk
for malignant neoplasms of the respiratory system for men
employed full-time top-side and the 1.70 relative risk (not
significant) for men employed less than 5 years suggest a
dose-response relationship, which Mazumdar (1975) further
substantiates by calculating cumulative exposures of the
cohort.to CTPV's. (These data are analyzed later.) Red-
mond's work also confirms the need to allow an adequate
induction period in study design, since workers with less
than 5 years experience at time of entry could have accumu-
lated only 20 years of total exposure at most.
Table 7 summarizes additional data (1967 to 1970)
analyzed by Redmond (1976). These data from the Allegheny
50
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County steel plants demonstrated a consistent increase in
the level of risk of malignant neoplasms with increased
exposure for each of the coke oven groups. Further, the
'- risk of side-oven workers for lung cancer, which had not
been statistically significant in the earlier studies,
reached significance (RR 1.79; p<0.05). Although no dose-
response relationship was apparent, the relative risk for
cancer of the pancreas and the relative risks for respira-
tory diseases other than cancer increased markedly with
length of exposure. Estimates of exposure levels for this
set of studies are discussed later.
'The latest study by Redmond et al (1976) again con-
firmed elevated risks for coke oven workers for lung cancer
(44 deaths vs. 24.5 expected; p<0.01) and genitourinary
cancer, relative risk 1.82 (p<0.05), due primarily to a 5-
fold increase in kidney cancer. Data on nonoven workers
continue to demonstrate excess kidney cancer, and the most
Decent studies in the Lloyd series show that incidences of
buccal and pharyngeal malignancies are highly significant.
Redmond's study also presents evidence that the ob-
served- elevated incidence of intestinal and pancreatic
cancer is not attributable to the country of origin of the
workers, an important consideration because studies of
j migrants have established differences in risk among those
51
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populations. The overall conclusion of the paper is that
"these observations indicate the need to consider nonoven
coke plant workers as well as oven workers when evaluating
cancer hazards in the plant." The health implications of
these data are discussed in Section 7.
\
52
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SECTION 6
•»
AMBIENT POLLUTION AND RESPIRATORY DISEASE
The effects of exposure to coke oven emissions among
the general population are not well understood. There are
no definitive epidemiological studies of low-level exposure
to coke oven emissions of populations near coke plants. A
recent paper (Graff and Lyon, 1977) reports findings near a
large coke oven in a northern Utah county. A statistically
significant excess of lung cancer cases (as compared to
controls) was found among residents living 4.8, 6.4 and 8
kilometers from the coke oven but not at points nearer (1.6
and 3.2 kilometers) and farther (16 and 24 kilometers) from
the oven. Only an abstract of this paper is available, and
without more information the results are difficult to inter-
pret.
Most of the pollutants that make up coke oven emissions
are present in urban air but in different proportions from
those found in the vicinity of coke ovens. Some studies on
urban air pollution have found that the lung cancel death
rate in urban areas is roughly twice that in rural areas
/ (NAS, 1972), and several studies have shown a correlation
53
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between the "urban factor" and BaP concentrations. Several
other studies, however, have failed to confirm such a corre-
lation (Carnow and Meier, 1973; Pike et al, 1975). There is
at present no consensus that the urban factor is general air
pollution (e.g., Higgins, 1977). For the purpose of this
document, no quantitative data are available on which to
base a judgment on the effects of low-level exposure to
coke oven emissions. In contrast to the controversy about
air pollution and lung cancer, there is substantial agree-
ment that air pollution contributes to the increased inci-
dence of both morbidity and mortality from nonmalignant lung
disease [much of this evidence is cited in a recent review
of air pollution and health by Goldsmith and Friberg (1977)],
For example, the College of General Practitioners Survey
(1961) in Great Britain has published data showing a 2- to
4-fold increase in the incidence of chronic bronchitis in
urban versus rural areas, a difference not completely
accounted for by the 2- to 3-fold increase in incidence of
chronic bronchitis attributed to smoking.
Buck and Brown (1964) found that particulate matter and
sulfur dioxide had high correlations with bronchitis mor-
tality, and Toyama (1964) found significant correlations
between bronchitis and dustfall in 21 Tokyo districts where
age-standardized mortality rates reflected increased levels
54
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of exposure. Nose (1960) reported a strong association of
bronchitis and pneumonia with dustfall in Ube, Japan.
Carnow et al (1970) correlated sulfur dioxide concentrations
with increased chronic bronchitis. Spicer et al (1962)
observed that respiratory symptoms in patients with chronic
bronchitis were associated with S0~ levels measured 38 hou1"?
previously. This finding was substantiated by McCarrol et
al (1967), who reported intervals of 24 hours and 48 hours
between the occurrence of sulfur dioxide and particulate
pollution and symptoms of respiratory ailment.
Winkelstein et al (1967), using mortality data from
Buffalo and Erie counties for the years 1959 to 1961, found
a positive association between air pollution, as indexed by
suspended particulate, and chronic respiratory disease.
A number of acute air pollution episodes, described by
Goldsmith and Friberg (1977), have demonstrated that an
extreme deterioration in air quality can have a serious
effect on human health. Most of these episodes occurred
when stagnant polluted air was trapped ovei a city for
several days during a temperature inversion. The numbers of
deaths and hospital admissions due to respiratory complica-
tions rose dramatically during these episodes, the greatest
number of cases occurring among older persons. During the
worst recorded episode (in London in 1952), the total excess
55
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of deaths was between 3500 and 4000, with bronchitis,
bronchopneumonia, and heart disease as the main causes of
death. The only common factor revealed by autopsy was
irritation of their respiratory tract (Ministry of Health;
London, England, 1954). In the London episode, as in other
episodes, the levels of sulfur dioxide and particulate
matter were exceedingly high.
Both general air pollution studies and the effects of
acute air pollution episodes suggest that bronchitis is
related to air pollution, but the parameters of a possible
dose-response relationship are not well defined.
56
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SECTION 7
ANALYSIS OF HEALTH'EFFECTS
INTRODUCTION
Assessment of the health effects attributable to the
array of toxic pollutants in coke oven emissions must be
based on quantitative and qualitative judgments. Qualita-
tively, it is clear that coke oven emissions represent a
serious carcinogenic risk to human beings. Extensive epi-
demiological evidence shows•that workers exposed to rela-
tively high levels of coke oven emissions develop cancer,
especially cancer of the respiratory tract, at rates sig-
nificantly higher than those reported for other workers and
for the general population.
The epidemiological evidence is confirmed by equally
powerful results of experimental bioassays, which show that
BaP is carcinogenic in all species tested by all routes of
administration (see Table Al for examples). Further, other
components of the emissions also induce cancer in test
animals, and combinations of the components are even more
effective in experimental induction of cancer (Hoffmann and
Wynder, 1976; Laskin et al, 1970). Dose-response relations
57
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are observed in these assays. An example of the dose-
response data is given in Figure 1.
Investigations of the binding of various PAH metabolites
to DNA have yielded additional evidence of potential human
health hazards (Gelboin, 1969; Sims et al, 1974; Huberman et
al, 1976). These findings have been supplemented bv posi-
tive Ames tests indicating the mutagenicity of various PAH's
as noted in Table A2. This microbiological assay system is
in many instances correlated with carcinogenicity
The data describing human experience, rests with
animals, and in vitro experiments constitute one body of
evidence. Further, it is known that the particulate size
distribution associated with coke oven emissions is optimum
for penetration and absorption into the human respiratory
system, and that the composition of the particulate matter
[hematite, (Saffiotti, et al, 1968); carbon, (Boren, 1964;
and others)] optimizes such absorption. Considered to-
gether, these facts lead to the conclusion that coke oven
emissions present a definite health hazard to persons ex-
posed to industrial concentrations.
Despite the strength of the eviuence, difficulties
arise in attempts to quantify the level of risk and to
extrapolate it to the population at large, who are exposed
to much lower levels of the pollutants. Part of the diffi-
58
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95
90
• 80
3 70
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5 40
S 30
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30 90
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270
[Source: Pott et al, 1977]
Figure 1. Dose-response relationships for mice and BaP
administered subcutaneously.
59
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culties are experimental, part theoretical, and a large part
philosophical. The problems are addressed systematically in
the following analysis.
BIOASSAY RESULTS
Although extensive experimental evidence shows that
many of the components of coke oven emissions are carcino-
genic, experimental carcinogenesis does not purport to
establish that a given factor contributes to cancer in man.
At present, such proof can be based only on epidemiological
data. The laboratory studies do allow us to identify the
chemical and physical nature of tumorigenic agents, to
explore their biological action and to devise means of
reducing their concentrations in or eliminating them from
our environment.
In the past 25 years considerable progress has been
made in developing organ-specific bioassay techniques, in
understanding damage to host defenses against toxic agents,
and in exploring the metabolic activation of environmental
carcinogens (Hoffmann and Wynder, 1976). Laboratory studies
support the concept that in only a few cases is a single
factor responsible for an increased risk of developing a
specific type of cancer and that cancer attributable to
environmental factors often is induced by the combined
effects of several agsnts (Van Duuren et al, 1969), Model
60
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studies have helped to explain the combined effects of
occupational factors, smoking, and urban pollution in in-
duction of cancer of the lung (Hoffmann and Wynder, 1976).
Experimental data are not adequate, however, to allow
determination of a safe dose for any chemical carcinogen,
below which there will be no tumorigenic response in humans.
Bioassays can be used to evaluate the carcinogenic potential
of various environmental agents by means of observed dose-
response relationships.
An abundance of in vivo and in vitro experimental
evidence confirms the carcinogenicity of various PAH's and
elucidates the roles of other PAH's, irritating substances,
a variety of solvents, and other factors in promoting and
initiating tumors and in cocarcinogenesis. These findings
are discussed in Section 4 and are detailed in Table Al. It
is important to note that in these studies all animal
species tested developed tumors in many sites by all routes
of administration.
CHARACTERIZATION DIFFICULTIES AND HEALTH EFFECTS
In addition to the widely recognized problems inherent
in extrapolating among species and in applying results of
experiments with animals to humans, the multiple and varied
constituents of coke oven emissions further complicate the
assessment of health effects.
61
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Most investigators of the carcinogenic effects of air
pollutants use BaP as an index of the level of carcinogens.
Many inaccuracies are inherent in a BaP index. Sawicki
(1967) notes that urban pollution from various sources is
characterized by different proportions of polycyclic arenes,
some carcinogenic and some not. However, some PAH's thought
to be noncarcinogenic alone may, in combinations with other
factors such as ultraviolet light, induce tumors. Thus,
Sawicki suggests that the nature of the mixture determines
its carcinogenicity for humans. This suggestion has been
verified in laboratory experiments (Van Duuren et al, 1969;
Laskin et al, 1970).
The problem of an accurate index need not be considered
if we treat "coke oven emissions" as whole and do not apply
an exposure index, such as the concentration of BaP or the
sum of the concentrations of several PAH's in extrapolating
health effects. Because the extensive epidemiological
evidence describes adverse health effects experienced by an
industrial work force exposed to "coke oven emissions"
(i.e., the total, complex mixture, often characterized as
the benzene-soluble fraction of the total particulate matter),
we need not delineate, for the human experience, the effects
of the constituents acting separately or in various combina-
tions with each Other. IT IS, THEREFORE, ESSENTIAL THAT THE
62
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ASSESSMENT OF HEALTH EFFECTS PRESENTED HERE BE APPLIED TO
"COKE OVEN EMISSIONS" AS AN ENTITY AND NOT TO ANY PARTICULAR
COMPONENT, SUCH AS BaP.
Other biological evidence supports the position that
coke oven emissions must be considered as a whole in evalua-
tion of health effects. For example, the association be-
tween lung cancer and cigarette smoking confirms the inter-
action of various factors in a complex mixture, since the
carcinogenicity of cigarette smoke cannot be explained by
the identified carcinogens alone (Hoffmann and Wynder,
1976) .
The similarity of the constituents of tobacco smoke and
those of coke oven effluents further supports the plausi-
bility of a dose-response relationship for coke oven emis-
sions, since there is such a relationship for cigarette
smoke (Table 9). The presence of irritants, toxicity pro-
moters, and cocarcinogens must play an important role in the
carcinogenicity of coke oven emissions as it does in ciga-
rette smoke since, as Table 10 shows, similar agents are
present in both mixtures.
The temperature of carbonization in cigarette smoking
is about 860°C, whereas in coal carbonization the tempera-
tures ranges from 1200 to 1400°C. As noted earlier, the
proportion of toxic compounds produced by carbonization
63
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Table 9. RELATIVE RISK FOR LUNG CANCER AS A FUNCTION
OF DAILY TAR DOSAGE FROM CIGARETTES IN MALE
SMOKERS WITH TEN YEARS OR MORE OF SMOKING3
Tar dosage,
mg
Up. to 340
341 - 480
481 - 630
631 - 1000
1001 and up
Non smokers
No. of
cigarettes/day
up to 20
20 - 29
29 - 37
37 - 59
59 and up
No. cases of
lung cancer
54
71
102
159
109
a
No. controls
247
231
216
270
197
509
Relative
risk<3
13.9
19.6
30.0
37.5
35.2
a Source: S. Stellman, in preparation.
k Average daily tar intake for the past 10 years.
0 E.G. a cigarette that contains 17 mg tar.
d Relative risk is defined as the incidence of disease in the exposed group
divided by the incidence of disease in the nonexposed group, as estimated
by the odds ratio.
64
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increases with an increase in temperature, and there is a
corresponding increase in the incidence of disease, as shown
in Table 4. The greater concentration of toxic substances
may explain why the observed incidence of lung cancer among
coke oven workers is equivalent to a risk 3 times that of a
person who smokes two packs of cigarettes per day. The
cancer rate among coke oven workers appears to be due not
just to the carcinogens but also to irritants and particu-
late matter. This fact is in accord with evidence of syner-
gism between irritants and carcinogens in animal studies
(Laskin et al, 1970; Saffiotti et al, 1968; Boren, 1964) and
with epidemiological evidence.
Despite the need to consider coke oven emissions as an
entity, some of the discussion and the experimental results
are, of course, based on exposures to BaP. This is inevi-
table because most scientific work relating to air pollution
relies on BaP as an indicator substance, although, in fact,
most environmental assays of coke oven emissions have dealt
with the benzene-soluble fraction of total particulate
matter (CTPV). To facilitate the interpretation of epide-
miological evidence, we sometimes "translate" CTPV values
into the corresponding BaP concentration units. The use of
BaP units is a method of converting the available data on
coke oven emissions, usually given as CTPV, into t\e same
67
-------
units given in most data on urban exposures, although the
ratio of constituents varies with the source.
The conversion of CTPV data to BaP units is not a
trivial or obvious procedure. As Sawicki (1967) notes,
there is a "tremendous range" in concentrations of airborne
particulates, benzene-soluble organics (BSD), and BaP in
various urban air samples. Figure 2a shows that a good
correlation between BaP and the benzene-soluble fraction of
CTPV can be obtained (Smith, 1971). As shown in Figure 2b,
the correlation between cyclohexane extracts and BaP is not
as good, particularly at low concentrations (Smith, 1971).
For purposes of this discussion, the concentration of BaP is
taken as 1 percent of the total organic fraction. This
approximation probably involves at most a 2-fold error and
is commonly applied by others (Schulte et al, 1975).
The validity of extrapolation and comparison of expo-
sure levels among various studies is limited even further by
the sampling method. A 2- to 4-fold margin of error is
probable in comparison of values obtained by high-volume air
samples with those obtained with a personal monitoring pump,
as demonstrated by Schulte et al (1975). Other sources
(White, 1975) believe that the error may be even greater.
Combinations of these errors, if they are acting in the same
direction, may lead to as much as 4- to 8-fold over- or
68
-------
25
20-
I15
bJ
§ 10
O.
S 5
r « 0.8415
2a.
1.0 2.0 3.0
BENZENE-SOLUBLE FRACTION, mg
BaP in benzene-soluble fraction of total particulate
matter.
. 30
r * 0.8539
WITH "OUTLIER"
REMOVED
(OBSERVATIONS£ 2 ONLY)
©
"OUTLIER"
3 4 S 6 7 8
CYCLOHEXANE-SOLUBLE FRACTION, mg
2b. BaP in cyclohexane-soluble fraction of total particu-
late matter. Insert shows no correlation for con-
centrations lower than 2 mg cyclohexane-solubje.
Figure 2. Least-squares fits of BaP in benezene- and
cyclohexane-soluble fractions of total particulate matter
[Source: Smith, 1971].
69
-------
underestimate of exposure to BaP. Since, however, we are
here dealing with differences of 3 to 5 orders of magnitude
in exposures of the general population and occupational
exposures to BaP (based on urban exposure levels due to coke
oven emissions as determined by Stanford Research Institute,
1977), a 4- to 8-fold range of error can be tolerated,'
although it is certainly not desirable.
BASES FOR INTERPRETING MORTALITY DATA
Overall and cancer mortality rates of the general
population are not readily applicable in evaluating the
effects on the general population of exposure to coke oven
emissions. First, if an increased rate of lung cancer among
the general population results from exposure to coke oven
emissions, such an increase may be masked by the very large
increase in lung cancer due to cigarette smoking. Although
coke oven emissions contain similar and possibly more
potent carcinogenic agents, the levels of pollution from
coke oven emissions in the general population, away from the
plant, are very much lower than those of cigarette smoke.
As Wynder and Hoffmann (1972) calculate, "heavily polluted
air" contains a maximum of 100,000 particles per cubic
centimeter of air as compared with 5 billion particles per
cubic meter in tobacco smoke, a difference of 5 orders of
magnitude. When the relative amounts of air breathed in are
70
-------
taken into account, a difference of about 2 orders of
magnitude remains.
The long period of induction for lung cancer, usually
15 to 30 years, increases the difficulties of correlating
urban air pollutants with lung carcinogenesis because of
such factors as urban mobility and .the inadequacies of both
air quality data and mortality data. For these reasons, it
is useful to examine the results of human high-level (occu-
pational) exposures in estimating the health effects of
exposure to coke oven emissions for the general population.
It is important to note that the overall mortality
experience of coke oven workers is better than that of the
general population, either urban or rural, in most epidem-
iological studies. This is typical of an industrial work
force and has come to be called the "healthy worker effect."
If a person is strong and healthy enough to be an industrial
worker, that person is part of a group that on the average
must be stronger and healthier than nonworkers and hence
experiences a more favorable mortality rate. Therefore,
because it is in direct contrast to an otherwise favorable
mortality rate, the unfavorable mortality rate for specific
causes of death such as all cancer, respiratory cancer,
bladder cancer, kidney cancer, and bronchitis among coke
oven workers as compared to others is of special interest.
71
-------
In general, caution must be exercised against "underinter-
preting" data and incompletely evaluating the magnitude of
the risk. As is shown in Table 7, as the period of observa-
tion increased, the relative risk or relative mortality also
increased. Further, as noted by Mazumdar (1975), the cur-
rent period of observation, on the average 20 years, is not
long enough to allow full assessment of magnitude of risk.
With these caveats in mind, we must attempt to establish
that the elevated mortality rates of coke oven workers can
be attributed to their exposure to coke oven 'emissions. In
his analysis of long-term mortality among steelworkers,
Lloyd (1971) develops criteria for interpreting excessive
mortality as a consequence of environmental exposures as
opposed to excessive mortality that can be associated with
selection for health; that is, the criteria should differen-
tiate between a true causative agent in a work area and the
movement of people into and out of a work area because of
health considerations. Lloyd states that if the excess
mortality is limited to a single organ system or a single
cause, then one would tend to suspect a causative factor in
the workplace environment. (The converse is not necessarily
true. If excess death from many causes is observed, one
cannot rule out the environment as a cause.)
72
-------
A second Lloyd criterion that can be useful in differ-
entiating effects due to occupational exposures from effects
associated with selection for health is that within certain
work areas excessive mortality is unaffected by race, na-
tivity, and residence.
When the Lloyd criteria are applied to the subgroup of
steelworkers who are employed at the coke ovens, it is
observed that, contrary to general mortality of steelworkers,
the reasoning he applied implicates environmental factors as
the cause of disease among coke oven workers. Since dis-
eases of one system, the respiratory system, and one disease
in particular, lung cancer, are the most prominent causes of
excessive mortality among coke oven workers, the first
criterion is fulfilled. The second criterion is also ful-
filled, since the mortality from cancer and respiratory
disease crosses bounds of race, nativity, and residence
among coke oven workers. Lloyd, of course, drew the same
conclusions, and he and others have been investigating the
experience of workers exposed to coke oven emissions.
ESTIMATING HEALTH EFFECTS FROM OCCUPATIONAL MORTALITY DATA
In assessing the health risk of coke plant workers and
its meaning for the general population, one must make sev-
eral approximations and assumptions. The problem of assem-
bling a comparison group for epidemiological investigations,
73
-------
especially those involving occupational exposures, is always
a great one, and the long-term mortality study of steel-
workers studies is no exception. As Table 8 shows, the
series of reports devoted to the mortality of coke plant
workers is based on the use of several different comparison
groups. In several studies the oven and nonoven workers
were compared with the entire steelworker population, then
steelworkers with no direct oven work experience but with
nonoven work experience in the coke plant, and finally, with
steelworkers with no coke plant exposure. A further dif-
ference in these studies is that some reports include more
workers employed prior to 1953 and others are limited to
workers employed in 1951-1955 (Redmond, 1972). Because the
studies involve different comparison groups as controls and
because the basic study population is not constant, it is
difficult to compare the relative risks cited in different
reports of the series.
In gauging the effects of coke oven emissions on coke
plant workers, it is instructive to compare the lung cancer
death rate of steelworkers having no coke plant experience
with that of the nonsmoking general population. In Redmond's
(1976) calculation of the risk for lung cancer among coke
oven workers, the population of steelworkers with no coke
plant exposure served as the control population. This
74
-------
population has a mortality rate greater than that of a
person in the 45-54 year age bracket who smokes two packs of
cigarettes per day and comparable to that of moderate and
heavy smokers in higher age brackets. In all age brackets
the mortality of steelworkers ffom lung cancer is 15- to
100-fold greater than that of nonsmokers. Table 11 shows
the age-specific mortality from lung cancer of steelworkers
per 100,000 person-years of exposure and the mortality rates
of cigarette smokers and nonsmokers. The data show that the
excess mortality of the coke oven workers from lung cancer
cannot be attributed solely to cigarette smoking.
the relative risk of lung cancer among coke oven
workers can be expressed using the nonsmoking general popu-
lation as a control. This is done by drawing on statistics
comparing the lung cancer death rate of two-pack-per-day
smokers and of the nonsmoking general population. Such an
approximation will overestimate the risk in the higher age
brackets where the steelworkers mortality is less than that
of a two-pack-per-day smoker, and will underestimate the
risk in the lower age brackets, where the steelworker lung
cancer mortality is greater than that of a two-pack-per-day
smoker.
The conversion (Table 12) of Remond's relative risks to
relative risks taking the nonsmoking general population as a
75
-------
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76
-------
Table 12. APPROXIMATE RELATIVE RISKS FOR THE NONSMOKING
POPULATION ESTIMATED FROM MORTALITY RATES FOR
COKE PLANT WORKERS3
Coke plant workers
.Coke oven workers
Nonoven workers
Relative Riaksb
Steelworker
comparison
1.93
3.19
0.95
Derived nonsmoker,
non»teelworker
comparison
32.0
53.0
15.8
a Data from Redmond (1976); Redmond, Strobino, Cypress (1976);
Hammond (1966) .
Derived relative _ death rate coke oven workers death rate 2 pack/day smoker
risk nonsmoker ~ death rate steelworkersdeath rate nonsmokers
where: death rate steelworkers = death rate 2 pack/day smoker.
77
-------
control is calculated by use of the following algorithm:
Derived death rate coke death rate 2 pack/
relative risk _ oven workers day stnokers
nonsmoker death ratex death rate
steelworkers nonsmokers
. (the death rate x (death rate
2 pack/day smokers) steelworkers)
Since the mortality rate of steelworkers shown in Table 11
is approximately that of the two-pack-per-day smokers, a
conversion factor for a comparison of steel-workers and
nonsmokers is derived from data compiled by Hammond (1966),
calculating age-specific mortality rates of smokers with
respect to nonsmokers. This relationship, of course, is not
rigorously true, but the error is certainly not inordinately
great and the formula may yield an underestimate, since the
steelworker mortality is greater that that of smokers, at
least in the 45-54 age bracket. The mortality ratio for
smokers over 40 years of age is used. This is equivalent to
a relative risk for lung cancer of 16.6 for smokers relative
to nonsmokers. Multiplying the data presented by Redmond
(NYAS, 1976) by this factor gives the data in Table 12.
It is clear that since mortality due to lung cancer is
considerably higher in the steelworker population than in
the nonsmoking population, use of the steelworker population
as a standard for evaluating coke plant workers, as is done
in this study, yields an underestimate. Although some of
78
-------
the elevated risk can be attributed to cigarette smoking,
this does not affect the argument because whatever its
cause, the mortality rate still exceeds that of the non-
smoking general population. When the elevated mortality
rate of steelworkers is taken into account, the relative
risks for nonoven workers and all coke plant workers for
death from lung cancer grow to 15.8 and 32.0, respectively.
Of course, some of the excess cancer observed among the coke
oven workers is also attributable to smoking, and thus the
mortality risks shown in the table cannot be attributed
so,lely to exposure to coke oven emissions. The true value
of the relative risk for lung cancer must lie between the
values presented here, which are as high as a 53-fold rela-
tive risk, and those in Redmond, which are at least a 16-
fold relative risk.
ESTIMATING EXPOSURE
Once revised mortality estimates are calculated it is,
of course, essential to estimate corresponding exposures to
etiological agents, in this case coke oven emissions. One
approach was applied to the gas production workers studied
by Doll (1952, 1965, 1972) and was carried out by Pike et al
(1974) .
"The carbonization workers were exposed to an estimated
2,000 ng/m3 BaP for about 22 percent of the year (as-
suming a 40 hour working week, 2 weeks paid leave, 1
79
-------
week sick leave); very roughly, the men were exposed to
the equivalent of 440 (2000 x 0.22) ng/m3 BaP general
air pollution. This exposure caused an extra 160/105
lung cancer cases, so that we may estimate assuming a
proportional effect, that each ng/m3 BaP causes 0.4/105
(160/10-* T 440) extra lung cancer cases per year. A
city with 50 ng/m3 BaP air pollution might, therefore
have an extra 18/10^ lung cancer cases per year. These
numbers are not negligible, although they are small
when compared, say, to smoking a pack of cigarettes
every day.
This estimate of a small, but not negligible, general
air pollution effect on lung cancer agrees with most
other epidemiologic evidence on the subject."
Another approach can be derived from studies of steel-
workers by Lloyd, Redmond, et al, who observed a dose-
response relationship among the cohort of coke oven workers.
(Table 7 summarizes some of the findings.) In an evaluation
of the cumulative exposure to CTPV's in the cohorts of these
studies, Mazumdar et al (1975) derived exposure histories
from occupational records and air quality measurements
conducted by the Pennsylvania Department of Health and thus
quantified the dose. The results obtained for nonwhite coke
oven workers are taken from Mazumdar and are presented in
Figure 3.
The cumulative exposures were calculated from an algor-
ithm combining length of time spent in various jobs with
average levels of CTPV's. The death rate was calculated by
the direct method of age adjustment using the nonwhite coke
oven workers as a control population. The second value on
80
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81
-------
the x-axis represents an estimate of the equivalent of BaP
exposure of the cohort calculated for the purposes of this
study and is not part of the original publication. The BaP
values are taken as 1 percent of the CTPV's, which gives an
estimate well within an order of magnitude of error.
It is interesting to contrast the results in Figure 3a
with those in Figure 3b, the plot of cumulative exposure
versus death rate for the white coke oven workers, in which
a dose response relationship was not originally apparent.
According to Mazumdar et al the failure to observe such a
relationship "may be due to the small numbers of white
workers in the high exposure categories. In neither case,
however, can one carry out a simple extrapolation from the
death rate in the figure to the death rate of the general
population because of the constraints of the age-adjustment
method used, in which the nonwhite coke oven worker popula-
tion served as the control.
It is possible to carry out a very approximate extrapo-
lation of the death rate observed in the coke oven worker
population to the death rate expected for the general popu-
lation. The statistics for nonwhite workers are used here
because it is among the nonwhites that the dose-response
relationship was observed. The age stratum 45 to 54 years
at time of entry into the study is selected because men in
82
-------
the age range of 45 to 70 would be the most likely to be
developing cancer and other diseases over the course of this
study. An expected death rate is derived from the U.S.
Vital Statistics, using 1960 data on age-specific, cause—
specific rates, for deaths of nonwhite males from all causes,
all malignant neoplasms (140-205), -and all respiratory
cancer (160-164). The rates for ages 45 to 54 and 55 to 64
are each applied to the number of workers at risk in each
exposure category, as calculated by Mazumdar (1975) . The
resulting expected numbers of deaths are averaged as fol-
lows:
(rate factor x (rate factor x
No. of no. at risk no. at risk
expected = 45-54 years) + 55-64 years)
deaths 2
The rate factor is the annual rate multiplied by 14.5, which
is an approximation of the number of years of observation,
which ranged from 13 to 16 years, depending on when the
worker entered the study. The factor is divided by 1000 to
allow comparison with the Mazumdar rate, which is given as
deaths per thousand. No corrections are made for adjusting
the number at risk to take into account those who had al-
ready died, which results' in only a very small underestimate
of the true number. The results of this calculation, given
in Table 13, represent the range of observed and expected
83
-------
Table 13. ESTIMATED CUMULATIVE EXPOSURE TO BaP AND
CTPV AND CORRESPONDING OBSERVED MORTALITY3
Cumulative exposure
mg/ra-months CTpv x
.ng/m3'month BaPb
Nonwhite coke oven
workers
Number at risk,
age 45-64
Overall mortality
Number of deaths
observed
Death rate/1000
Estimated expected
deaths0
Observed/estimated
expected
Cancer, all sites
Number of deaths
observed
Death rate/1000
Estimated expected
deathsc
Observed/estimated
expected
Lung cancer
Number of deaths
observed
Death rate/1000
Estimated expected
deaths0
Observed /estimated
expected
<1.99
54
14
259. 2
18.4
0.761
3
55.6
3.07
0.977
1
18.5
0.497
2.01
2.00-4.99
151
4B
317.9
51.5
0.932
11
72.9
8.57
1.28
3
19.9
1.39
2.16
5.00-6.99
108
30
277.8
36.9
0.813
10
92.6
6.13
1.63
5
46.3
0.993
5.03
7.00 +
155
45
290.3
52.9
0.851
19
122.6
8.60
2.16
8
51.6
1.43
5.59
Total
nonwhite oven
workers
468
137
292.7
159.6
0.858
43
91.9
26.6
1.62
17
36. 3
4.30
3.95
* Age-adjusted, age-specific death rates for overall mortality, cancer of all
sites, and lung cancer, based on mortality observed from 1951-1966 for nonwhite
coke plant workers, by estimated cumulative exposure to BaP and CTPV, and age
of entry into study. Expected rates are derived from average of U.S. age-
specific mortality by cause for nonwhite males aged 45-54 «nd 55-64 with
approximated average of exposure time of 14.5 years. Adapted from Mazumdar
(1975).
Derived from mg/m of coal tar pitch volatiles.
c Estimated from average cause and age-specific U.S. mortality rate, 1960, for
age brackets 45-54, 55-64 over estimated average exposure of 14.5 years.
84
-------
deaths for each of the exposure categories. Figure 4 also
compares observed and expected deaths.
It should again be noted that as in other calculations,
overall mortality of the coke oven workers is more favorable
than that of the general population, and respiratory cancers
again account for a relatively large proportion of the total
cancer mortality. Although the ratio of observed/expected
overall mortality in this calculation is highly approximate,
it can serve as the basis of a crude measure of the esti-
mated increase in mortality rate of the general population
if they were exposed to lifetime dosages similar to those of
coke oven workers.
Each of the columns in Table 13 represents a cumulative
exposure in mg/m 'months for members of the work force, as
calculated by Mazumdar. For estimation purposes we can
calculate equivalent exposures for the general population.
By setting arbitrary durations of exposure, say 60 months,
the ambient levels needed to achieve a particular cumulative
exposure are obtained simply by dividing the exposure by the
duration. In this way one can determine the ambient con-
centration that, over a period of time (e.g., 5 years, 60
months), would give a total exposure equivalent to that
experienced by the various segments of the cohort in the
Mazumdar study.
85
-------
s
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86
-------
Lifetime cumulative exposure = j^^ concentration level
Hypothesized duration
For example:
mg/m *months .3
* months = mg/m
(The CTPV values are converted to BaP concentrations by
multiplying by 1 percent, as previously.)
Performing this calculation for the time periods of 5
years (60 months) to 50 years (600 months) yields the levels
given in Table 14. These levels range from a low of 3.32
3 3
yg/m BaP to a high of 116.7 yg/m . Each column represents
the concentration necessary for the given time period in the
left hand column to yield lifetime dose equivalent to that
experienced by coke oven workers. These equivalent exposure
values can be compared with the exposures of the general
population to BaP and coke oven emissions when assessing the
risk to the general population.
Although it is difficult to extrapolate an exact ex-
pected rate, the following should be kept in mind. First,
the cancer rates observed in the studies discussed here
represent the minimum increase in rate because the period of
observation has been only 14 to 16 years and Mazumdar's
"...data indicate that the time between first exposure to
coal tar pitch volatiles and death from lung cancer varies
from 10 to 40 years, with an average of 25 years." Second,
the exposure values are inaccurate because of the sampling
87
-------
Table 14. ESTIMATION OF EQUIVALENT LIFETIME DOSE FOR
THE GENERAL POPULATION3
Lifetime
exposure
(i/g BaP-Months) ,
m3 x 10
Duration,
months
60
120
180
240
300
360
420
480
540
600
yg BaP/m x 10 -months
11.99
2.00-4.99
(calc. as 3)
5.00-6.99
(calc. as 6)
7.10
Calculated concentration leading to lifetime dose,
yg/m3
33.2
16.6
11.1
8.29
6.63
5.53
4.74
4.15
3.69
3.32
58.3
29.2
19.4
14.6
11.7
9.72
8.33
7.29
6.48
5.83
100
50
33.3
25.0
20.0
16.7
14.3
12.5
11.1
10
116.7
58.3
38.9
29.2
23.3
19.4
16.6
14.6
13.0
11.7
Values calculated represent the ambient air levels required
to achieve the lifetime dose listed for the hypothetical
time periods shown in the first column.
88
-------
and analysis problems discussed earlier. If the combination
of insufficient observation time and sampling error togethoi
act toward underestimation, the actual increased risk of I ho
exposed population may be much greater than the calcul if ions
show.
Comparison of the ambient data calculated by the n'.m
ford Research Institute (SRI) with the calculated ambi . i
data in Table 14 shows that a value of 10 to 15 ng/m , '.
median value given by SRI, which is within about 2-1/•
orders of magnitude of the lowest level in Table 14, .
in at least a doubling of the lung cancer rate. Pot-
stated earlier, this rate is assuredly an underestimai -
NONMALIGNANT RESPIRATORY DISEASE
Several mortality studies have shown that worker :;
coke plants are at an increased risk for dying of chr<*<
bronchitis. Unlike the risks from respiratory malign,u.^y
the risk appears to be about the same for coke oven wot'
and for nonoven workers employed at the coke plant. i" .
data, summarized in Table 15c, show that tne risk of c< '<-.
plant workers is significant and is greater than 2-foM
relative to the rate of mortality from chronic bronchi1
the steelworker population.
Doll (1965, 1972) has observed a similar excess ,,
ity from chronic bronchitis among gas retort workeid. :*.
89
-------
Table 15. OBSERVED BRONCHITIS MORTALITY
A. Standardized annual death rate per 1000 men for bronchitis; all gas
boards grouped together and England and Wales, 1953-61."
Occupational Class
A
2.89
B
1.34
Cl
1.94
C2
1.19
C
1.28
All Classes
1.62
England and
Wales
1.36
Class A « heavy exposure in carbonizing plants; Class B =
intermittent exposure to conditions in other gas-producing
plants; Class Cj « exposure only to by-products, i.e. process
and maintenance workers in chemical and by-products plant.
Class C2 • minimal or no exposure, i.e. all other employees;
Class C
2'
B. Numbers of deaths from bronchitis and in each occupational class and
numbers expected from the experience of all gasworkers, allowing for
age and employing board.3
Occupational Class
A
Observed
49
Expected
28.54
B
Observed
40
Expected
47.33
C
Observed
52
Expected
65.13
Probability
of trend
arising due
to chance
<0.001
C. Observed deaths and relative risks of death from nonmalignant
respiratory diseases, 1953-1970, for coke plant workers by work
area and length of employment through 1953.^
Work Area
Total coke plant
Coke oven
Nonoven
No one coke
plant area
Years employed throuq
5+
Obs.
34
20
14
0
RR
1.47C
1.47
1.45
e
10*
Obs.
31
17
14
0
PR
1.82d
1.92C
1.75
e
h 1953
154
Obs.
25
12
13
0
RR
2.01d
2.20C
2.07C
e
a Adapted from Doll (1965).
b from Redmond (1976).
c p <.05.
less then 5 deaths,
90
-------
these studies the risk again extended to men with heavy and
light exposures to the effluent from the retorts. These
data, tabulated in Table 15b, indicate the same magnitude of
risk as that observed in the studies of Lloyd, Redmond et
al.
Mortality rates for nonmalignant respiratory disease
constitute an incomplete assessment of any potential cor-
relation between occupational exposure to coke oven emis-
•
sions and chronic bronchitis and emphysema. This is so
because, unlike lung cancer, from which mortality is ex-
tremely high, other chronic lung disease is not necessarily
fatal. A better measure of the effects of coke oven emis-
sions in producing nonmalignant respiratory disease is a
combination of increased incidence of both morbidity and
mortality. An increase in incidence of both morbidity and
mortality has been observed in several investigations of the
chronic bronchitis rate of coke plant workers.
Adequate morbidity data for nonmalignant respiratory
disease are difficult to obtain. Whereas lung cancer has
been readily diagnosed for at least the last 30 years, some
cases of chronic bronchitis very probably remain undiagnosed
(Ferris, 1973). Also, chronic bronchitis is not a reportable
disease. For this reason, observations of bronchitis and
other nonmalignant respiratory disease therefore usually
91
-------
entail monitoring and medical surveys of working popula-
tions, from which retirees are most often excluded.
In light of the combination of the relatively low rate
of fatality from nonmalignant respiratory disease, the
competitive risk from other diseases associated with coke
oven exposure, and the difficulties of estimating incidence,
the true incidence of such nonmalignant respiratory disease
must be greater than the sum of the morbidity and mortality
data presented here. Coke plant workers are both healthier
than the general population and younger than the population
at greatest risk for chronic bronchitis, among whom are the
elderly. The very young are also highly susceptible to
bronchitis. The increased mortality among coke plant
workers from this disease therefore indicates that coke oven
emissions pose a powerful hazard to the respiratory systems
of exposed workers.
MORBIDITY STATISTICS
A consideration in assessment of risk for bronchitis
among coke plant workers is that these workers have been
"selected" for tolerance to sulfur dioxide mixed with par-
ticulates, both constituents of coke oven emissions. It has
been estimated that 10 to 20 percent of healthy young adults
show susceptibility to industrial levels of SO- (Burton et
al, 1969) and are unable to work at jobs involving exposure.
92
-------
This means that the workers who are included in epidemio-
logical studies are those who can tolerate industrial levels
of S02 and can be considered to be less sensitive to, or
able to adapt to, these levels, as noted by Amdur (1969).
If this relatively "SC>2 resistant" portion of the work force
is showing an increased rate of bronchitis, it is prudent to
assume that lower levels will produce similar effects on the
general population, which includes those who are at elevated
risk for bronchitis by virtue of age, pre-existing con-
ditions, or other factors.
Mittman et al (1974) in a survey of the incidence of
chronic bronchitis among 246 coke plant workers, found that
33 percent of the workers complained of symptoms and 17
percent were classified as having varying degrees of chronic
bronchitis, defined by standard criteria for sputum produc-
tion and dyspnea. The authors conclude that consumption of
cigarettes by the entire group was related to the severity
of symptoms, and they emphasize the need for more data on
the influence of smoking and on genetic susceptibility as
factors in occupational disease. Despite the authors'
emphasis on genetics and smoking, careful examination of
their data reveals that exposure to coke oven emissions
(that is, the index of job exposure) is the most significant
correlate for the occurrence of pulmonary disease.
93
-------
The analysis of Mittman et al is summarized in Table
16. Three groups of workers were tested for symptoms of
chronic bronchitis and smoking, work exposure history, and
genetic susceptibility (as determined by serum trypsin
inhibitory characteristics [STIC] and Pi phenotypes).
Simple correlation coefficients were calculated. The worker
groups were 1) all 246 coke oven workers in the study; 2) 81
men with symptoms and 20 men chosen at random; 3) 42 men
with diagnosed chronic bronchitis. Even though the authors'
conclusion that the incidence of chronic bronchitis of the
entire group tested is not significantly correlated to job
exposure is valid, it is important that the calculated index
of total job exposure was the only statistically significant
measure among the third group tested, those with chronic
bronchitis. Furthermore, the index for total job exposure
is the correlate that explains the largest percentage of
variability shown in the study; about 25 percent of the
bronchitis was explained by total job exposure. It should
also be noted that in this group cigarette smoking was not a
statistically significant variable, accounting for only
about 0.5 percent of the disease.
Among the second group of workers cigarette smoking and
work experience were of comparable statistical significance
and explained the same small percentage of variability in
the data.
94
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The apparent inconsistency of the results may stem from
the inclusion in the overall group of many workers with only
a few years of heavy exposure to substances that cause
chronic bronchitis. This would dilute the incidence of
disease and decrease the possiblity of observing an effect
of working conditions on pulmonary disease. This effect of
duration of exposure is consistent with the results of other
studies. The reports of Lloyd and others (Table 15) indi-
cated that chronic bronchitis mortality increased by 33
percent after 10 years of additional followup and also
reached statistical significance. Unfortunately, because
Mittman et al do not present data on the distribution of
workers according to exposure or to years of work, this
hypothesis cannot be independently confirmed or denied.
Walker et al (1971), in a study of bronchitis among
British coke plant workers, observed that of 112 men who had
worked for 1 year or more in the vicinity of the oven, 18.8
percent (26) had bronchitis, defined by productive phlegm,
as compared with 11.3 percent (27 out of 212) of the other
coke plant workers. The authors found a strong correlation
between prevalance of bronchitis and cigarette smoking, and
they suggest that smoking, a combination of smoking and
exposure to coke oven emissions, and previous employment in
dusty industry (e.g., coal mining) all have an important
96
-------
effect on the incidence of bronchitis. "Ovenmen" in this
study were defined as workers who had spent 1 year or more
in the environment of the coke ovens. The effect of long-
term exposure to coke oven emissions on the incidence of
bronchitis is difficult to determine because the study gives
no data on the length of exposures of the oven men and
nonoyen men.
The work of Lloyd, Redmond, Doll, and others indicates
that both oven workers and nonoven workers are at risk for
nonmalignant respiratory disease. It may be that those
suffering the greatest risk are cigarette smokers. However,
when the data presented by Walker are examined for the
incidence of chronic bronchitis among nonsmokers, ex-smokers,
pipe smokers, and light smokers (1 to 10 cigarettes per
day), analysis shows that this mixed group having less
exposure to cigarette smoke also experiences a significant
incidence of chronic bronchitis, about 43 percent, as shown
in Table 17. The table also shows the observed relationship
between age and bronchitis incidence. The incidence of
bronchitis among relatively young men should be noted.
Walker et al conclude that some adverse effects appar-
ently are due to a combination of smoking and history of
earlier exposure to a dusty environment, and that inclusion
of workers with only 1 year exposure in the study population
97
-------
Table 17. CHRONIC BRONCHITIS IN THE COKE INDUSTRY0
A. Incidence and smoking habits
Nonsmokers, ex-smokers (all workers)
Norrsmokers, ex-smokers (all
workers over 25 yr old)
Light smokers (1-10 cigarettes/day)
Pipe smokers
Total
No. of men
242
224 •
150
52
444
Bronchitis
No.
16
16
40
5
61
%
6.6
7.1
26.7
9.6
42.9
B. Incidence and age
Age, yr
No bronchitis
Bronchitis
Total
15-24
No,
51
2
53
%
96.2
3.8
100.0
25-34
No,
119
17
214
t
87.5
12.5
100.9
.35-44
No.
184
30
214
%
86.0
14.0
100.0
45-54
No.
206
57
263
t
78.3
21.7
100.0
55-64
No.
152
63
214
%
70.7
29.3
100.0
All ages
No.
712
169
881
%
80.8
19.2
100.0
Adapted from: Walker ct al (1971).
98
-------
may produce an underestimate. Thus, the report can be taken
as further evidence of a risk of bronchitis among workers
exposed to coke oven emissions and as evidence of the com-
plexity of interactions of such various etiologic agents as
smoking, job exposure, and previous history.
Since the elevated risk in all the studies discussed
here appears to be coke-plant-wide, it is not unreasonable
to extrapolate the health effects for the general population
from the effects observed for those in the study group with
the lowest exposure to the emissions, the nonoven workers at
the coke plants. This means that workers exposed to the
constellation of factors that make up coke oven emissions
(e.g., particulate matter, sulfur dioxide, PAH) at levels
well below those that are normally associated with "exposure"
suffer a significantly increased risk of developing non-
malignant respiratory disease, an irreversible, debilitating
condition. Levels of BaP measured at the periphery of coke
plants have been as low as 150 ng/m (Jackson et al, 1974),
a value that is within one to two orders of magnitude of
general population exposure levels presented by SRI.
99
-------
APPENDIX A
SELECTED BIOASSAY RESULTS
100
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106
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APPENDIX B
SOURCE AND CONCENTRATION DATA
107
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110
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Table B2. MINOR CONSTITUENTS OF COKE OVEN GAS
Substance
Concentration,
Country
HCN
NO
Dust
Benzo(a)pyrene
Benzene
Toluene
Xylene
2,000-4,000
1,300-3,000
120
0.8-4.9
22
16-24
3.5-4.5
1,800-36,000
334 ave
158-515
190-630
35,800
23,900
21,400
3,000
1,520
500
Czechoslovakia
USSR
West Germany
USSR
USSR
USSR
USSR
West Germany
USSR
USSR
USSR
USSR
USSR
West Germany
USSR
West Germany
USSR
Source: White et al.
Ill
-------
Table B3. ESTIMATED ATMOSPHERIC EMISSIONS FROM
COKE PLANTS IN POLAND AND CZECHOSLOVAKIA
Type of
emission
Dust
Tar
so2
CO
NH3
H2S
HCN
NO
Phenols
Benzene
Coke production
Emissions in
Poland (1966),
tons
16,039
8,565
40,385
5,457
1,702
1,794
166
351
13 million
Emissions in
Czechoslovakia (1968) ,
tons
9,900
13,000
3,030
950
990
99
990
1,660
4 million
Source: .White et al.
112
-------
Table B4. COMPARISON OF SELECTED POLLUTANTS AT
TOP-SIDE WORKPLACES IN THE SOVIET UNION
(concentrations, mg/m^)
Pollutant
NH3
CO
Cyanides
Pyridine Bases
Phenols
Benzo(a)pyrene
Conventional charging
6.3-8
40-74
0.9-3.6
0.17
0.14
0.0718
Smokeless charging
3.5-4.4
6-18
0.3-0.4
0.02
J.07
0.0177
Table B5. CONTENT OF NOXIOUS POLLUTANTS IN THE WORKPLACE
ENVIRONMENT OF CZECHOSLOVAKIAN COKING PLANTS
(concentrations, mg/rn^)
Compound
Benzene
CO
HCN
so2
Top-side
0.1-13.0
1.0-36
0.0-0.4
0.1-4.7
Side
0.0-0.2
0.0-0.5
0.0-0.1
0.0-0.2
Source: White et al,
113
-------
Table B6. CONCENTRATION OF PYRIDINE AND ITS HOMOLOGUES
AT WORKSITES IN CZECHOSLOVAKIA
(yg/m3)
Compound
Pyridine
2-Methylpyridine
3-Methylpyridine
4-Methylpyridine
2 , 5-Dimethylpyridine
2 , 6-Dimethylpyridine
Coal coke battery
155-1854
348-8256
73-402
47-289
47-107
48-903
Pitch coke battery
222-827
2100-4157
110-413
112-337
114-455
210-572
Table B7. Shi^CTED VAPOR CONCENTRATIONS IN THE COKE-OVEN
BATTERY ENVIRONMENT AT FIVE PLANTS IN THE UNITED STATES
(mg/m3)
Compound
Benzene
Toluene
Xylene
Naphthalene
Mean
9.5
0.6
0.3
0.7
Maximum
162.7
1.38
1.03
1.31
OSHA TLV
34.3
800
435
50
Source: White et al.
114
-------
Table B8. COMPARISON OF SELECTED PARTICULATE CONCENTRATIONS
Country
Concentration, ing/m"
Czechoslovakia
USSR
USSR
England
USA
Czechoslovakia
Czechoslovakia
Czechoslovakia
USA
USA
USA
England.
England
Czechoslovakia
(continued)
Charging levels
(conventional)
(smokeless)
(conventional)
(smokeless)
(catwalk)
Top-side levels
(total particulate)
(respirable)
(total particulate)
(respirable)
(total particulate)
(respirable)
Battery side levels
(pusher)
(coke car)
1.13-113
173.3
15.4-38.9
143-851
1-57
374.3
39.1-84.2
8.3-17.35(13.3 ave)
1.9-40.8
1.1-78.8 (15.2 ave)
0.28-9.22 (3.34 ave)
2.6-6.9
0.35-84.2 (8.05 ave)
26.7-64
4.1-15.7
0.6-1.7
5.1-8.5
1.7-3.7
0.4-395
1-136
115
-------
Table ~B8 (continued)
Country
Concentration, mg/m"
USSR
USA
OSA
5QO meters from battery
Cigarette smoke
Urban levels
1965
1.2-2.7
95,000
up to 1.254
(0.105 ave)
Source: White et al.
116
-------
%
CS 1*0
0 E
4-» 0
concentre
yg/100
c
4J
;oncentra
yg/m3
«1
Compounc
1
Detroit
D
D
Norway
Czech
England
OS
W
W
D
•P
•H
U
o
Country
00
•H
in
rH
(NJ 1
rH VO H
VO
m
VO
rH
1
CM
in
rH
rH
1
VO
0)
c
0) 0)
c a) x;
-------
Table BIO. COMPARISON OF BENZO(a)PYRENE CONCENTRATIONS
MEASURED AT COKE-OVEN BATTERIES AND AT OTHER SELECTED SITES
Country
Year
Concentration.
Top-side
Side
Soviet Union
Soviet Union
Japan
Norway
Czechoslovakia
Czechoslovakia
Czechoslovakia
Czechoslovakia
England
USA
USA
USA
USA
USA
USA
USA
Switzerland
USSR
England
England
USA
USA
1962
1968
1968
1959
1966
1967
1968
1974
1965
1974
1960
1974
1974
1968
1961
1961
1961
1966
1965
1965
1959
1966
1.27-27.4
0.05-7.38 (3.84)a
2-7.3
1.1-94.8
3.6-32.2
10.7-12.7
0.1-13.1
3-216
1.2-15.9 (6.5)
8.3-51
0-225.9
0.18-36.3 (5.78)
95
6.1
14-78
640
13.7-22
(0.02)
2330
(0.022)
(0.0185)
0.08-0.27 (0.17)
1.5-3.14
0.6-3.4
0.3-1.98 (1.0)
(9.55)
Contrast
Cigarette smoke
Auto exhaust
Roof tarring
Roof tarring
Aluminum Plant
Urban - London
Maximum found in
fumes emitted from
coke ovens
Birmingham
Birmingham
Mean.
Source: White et al.
118
-------
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